New Insights Into The Activation of The Immune System in Lupus

An international team of researchers recently published in the journal Nature Materials new findings on the activation of the body’s immune response in autoimmune disorders like systemic lupus erythematosus (SLE) and psoriasis. The study is entitled “Liquid-crystalline ordering of antimicrobial peptide–DNA complexes controls TLR9 activation”.

Autoimmune diseases are characterized by an overreaction of the body’s own immune system that leads to the attack of healthy tissues, including joints and organs, resulting in inflammation, pain, disability and often in tissue destruction. The causes underlying autoimmune diseases are poorly understood. Two examples of autoimmune disorders are lupus (SLE), which can result in skin, joints and organ damage, rashes, hair loss and fatigue; and psoriasis, a disorder characterized by skin lesions, rashes and arthritis.

Double-stranded DNA, in the instance of a virus, can be recognized by a cellular receptor called TLR9 triggering a defensive immune response through the production of important key proteins – type I interferon (IFN). In patients with lupus or psoriasis, the immune response is triggered by self-DNA, DNA from the patient.

In this study, using a combination of synchrotron X-ray scattering (a technique to determine how atoms and molecules are organized into different structures), microscopy, computer simulations and measurements of IFN production, researchers found that a broad range of molecules can assemble self-DNA into a liquid crystalline structure that is able to strongly bind to the TLR9 receptor. This structure protects the DNA molecule from degradation and greatly amplifies the body’s immune response.

“Our colleagues had established empirically that certain molecules were activating self-DNA and triggering responses in disorders such as lupus and psoriasis. We were able to elucidate something that was poorly understood — a key to triggering the immune response is that the molecules must arrange the DNA so that the receptors bind to them strongly.” explained the study’s co-lead author Dr. Nathan W. Schmidt from the University of California, Los Angeles (UCLA) in a news release.

The authors believe that their findings can be useful to develop new strategies to treat autoimmune disorders. “Our research has identified a set of rules that tell us what types of molecules or materials can set off this aspect of the immune system,” said the study’s co-senior author Dr. Gerard C. L. Wong from UCLA. “This new knowledge will make it easier to design new therapeutic strategies to control immune responses.”